Electrically-excitable cells include not only neurons and neuroendocrine cells (i.e. pancreatic islet β-cells), but also cardiac and muscle cells. The electrical activity (membrane potential) of these excitable cells is regulated by membrane ion channels which effect either membrane depolarization or repolarization.
The KATP channel has been best studied in the pancreatic islet β-cell1,11,12 whereby glucose entry and metabolism into the islet β-cell generates a change in the ratio of adenine nucleotides, adenosine trisphosphate (ATP) and adenosine diphosphate (ADP). Increased ATP and decreased ADP cause a closure of the plasma membrane KATP channel proteins. The resulting cell membrane depolarization then causes the opening of Ca2+ channels which effects Ca2+ influx into the cell to act on a set of SNARE proteins on the insulin secretory granules and plasma membrane which come together to form a complex that induces the fusion of the granule to the membrane and subsequent release of insulin.
In the normal cardiac muscle, the KATP channels are closed by the high intracellular ATP concentrations [ATP].2,13 However, during ischemia, the [ATP] are lowered, and results in the opening of KATP channels, and the resulting increase in outward K+ currents shortens the duration of membrane action potentials, leading to a reduction of Ca2+ influx, and consequent reduced contraction and energy consumption. The KATP channel opening therefore serves to protect the myocardium from ischemic injury.2,13 
These KATP channels are each composed of two distinct subunits, SUR and a member of the inward rectifying KATP channel family, Kir6.X, which is the actual gating pore.1 There are several isoforms of SUR.1 SUR1A (1581 aa, 177 kDa) is the dominant isoform in pancreatic islets and brain,3 SUR 2A4,5 (1545 aa, 174 kD) in the heart and skeletal muscle, SUR2B4,5,7 (1546 aa, 175 kD) in smooth muscle and vascular smooth muscle and the more ubiquitously expressed SUR2C (1512 aa, 170 kD).5 Kir6.X2,6-8 has two isoforms including Kir6.1 in smooth muscle and Kir6.2 in cardiac and skeletal muscles, pancreatic islets and brain. These SUR and Kir6.X proteins come together (i.e. SUR1A/Kir6.2, SUR2A/Kir6.2, SUR2B/Kir6.1) to form hetero-octamer (4SUR+4Kir6.X)1,14 proteins in the native cell plasma membrane. Each of the SUR proteins contains two large (180-200 aa) cytoplasmic folds (NBF1 and NBF2) each of which contains Walker A (WA) and Walker B (WB) motifs (FIG. 1).1 The Walker motifs form nucleotide binding pockets (hence called nucleotide binding fold-NBF). Much is known about the SUR1/Kir6.2 structure-function, as these were the first to be cloned,3,6,8 and because of its presence in islet β-cells and consequent therapeutic relevance to diabetes.1 Genetic mutations for the disease familial persistent hyperinsulinemic hypoglycemia of infancy PHHI15 were identified (G1479R in NBF2) within SUR1 to cause the pathologic closure of the KATP channel. Discovery of such mutations further contributed to the elucidation of the structure-function of SUR1. However, no such mutations have been found with SUR2. In both SUR1 and SUR2, ATP closes the KATP channel by binding to the SUR subunit, as well as Kir6.2.1.6,17 Upon ATP hydrolysis to ADP, the ADP in combination with Mg2+, opens the KATP channel mainly by binding to NBF2.8,20 Both NBFs act cooperatively to modulate not only MgADP binding and activity, but also Kir6.2 regulation by ATP.1 In fact, early studies showed that ATP has a secondary, albeit non-essential, binding site at NBF1 which prolongs KATP opening.21 
Overall, there is a 68% homology between SUR1 and SUR2A at the amino acid level,4 and the heterogeneity is attributed to the N-terminal transmembrane and the very C-terminal domains.22 Of a total of 17 transmembrane segments, the N-terminal five transmembrane helical domain confers the distinct binding affinity to sulfonylureas (100× higher affinity to SUR1>SUR2A) and burst intervals (shorter for SUR1 than SUR2A).4,22 In contrast, the NBF1 and NBF2 domains between the SUR1 and SUR2A possess very high homology.4 At the amino acid level, SUR1-NBF1 (aa 694-893) and SUR2A-NBF1 (aa 682-873) has a 81.4% homology, whereas SUR1-NBF2 (aa 1356-1535) and SUR2A-NBF2 (1320-1499) has a 86.6% homology.4 SUR2 has 3 alternatively spliced variants, SUR2A, SUR2B and SUR2C.1 SUR2A and SUR2B differ only in the last 42 amino acids at the C-terminus which is just outside the NBF2 region.4,22 Interestingly the C-terminal 42 aa domain of SUR2B is more similar to that in SUR1 (aa 1539-1581).7 The distinct C-terminus (42 aa) of the SURs confers the different ATP sensitivity22 (4-fold higher ATP sensitivity in SUR1 than SUR2A and SUR2B) and MgADP actions23 (increases potassium channel opener (KCO) binding to SUR2A, inhibits KCO binding to SUR2B24). Compared to SUR2A, SUR2C has a 35 amino acid deletion just outside the N-terminal end of NBF1 which corresponds to aa 635-670 region of SUR2A,5 and this region is interestingly also the most divergent region between SUR2A and SUR1.4 The NBF1s and NBF2s are therefore very well conserved between the SUR1 and SUR2 isoforms.
There has not been a ternary protein found to bind and regulate SUR or Kir6.2 in an ATP- and/or ADP-dependent manner.